Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach


Scaffold varied dihydropyrimidone derivatives 120 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (Ki values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 120 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic.

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The authors are thankful to Higher Education Commission (HEC) Pakistan for financial support under “National Research Support Program for Universities” (Project No. 5079) and King Fahad University of Petroleum and Minerals (KFUPM) Saudi Arabia (Project No. SB191017).

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Correspondence to Muhammad Arif Lodhi or Ajmal Khan.

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Khan, F.A., Shamim, S., Ullah, N. et al. Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach. Med Chem Res 30, 120–132 (2021). https://doi.org/10.1007/s00044-020-02643-z

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  • Dihydropyrimidones
  • Enzyme kinetics
  • Michaelis–Menten kinetics
  • Neutrophil based cytotoxicity
  • Phytotoxicity